1α,25-二羟基维生素D3抑制人结肠癌细胞系SW480中β-catenin转录活性  

1α,25-Dihydroxyvitamin D3 inhibitsβ-catenin transcriptional activity in human colon cancer cell line SW480

作　　者：辛玉[1] 贺龙梅 杨红[1] 吕红[1] 谭蓓[1] 汪红英 钱家鸣[1] XIN Yu;HE Long-mei;YANG Hong;LYU Hong;TAN Bei;WANG Hong-ying;QIAN Jia-ming(Department of Gastroenterology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730;National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, CAMS & PUMC, Beijing 100021, China)

机构地区：[1]中国医学科学院,北京协和医学院北京协和医院消化内科,北京100730 [2]中国医学科学院,北京协和医学院,肿瘤医院,国家癌症中心,国家肿瘤临床医学研究中心,北京100021

出　　处：《基础医学与临床》2020年第9期1169-1174,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81570505);山东省自然科学基金(ZR2019PH081);山东省重点研发计划(2017G006030)。

摘　　要：目的探讨1α,25-二羟基维生素D3[1,25(OH)2D3]对人结肠癌细胞系SW480中β-catenin转录活性的影响及作用机制。方法1,25(OH)2D3(100 nmol/L)干预和溶剂对照处理SW480细胞48 h;用双荧光素酶报告系统检测β-catenin的转录活性;Western blot检测1,25(OH)2D3干预后β-catenin在细胞核/质内的定位变化;用RT-qPCR和Western blot检测β-catenin和FOXM1 mRNA及蛋白水平。采用siRNA敲降SW480细胞中FOXM1后,检测1,25(OH)2D3干预后β-catenin转录活性的变化。结果1)在SW480细胞中,1,25(OH)2D3能显著降低β-catenin的转录活性(P<0.05),但不影响β-catenin mRNA和蛋白表达水平;2)1,25(OH)2D3上调SW480细胞中FOXM1蛋白水平的表达(P<0.05);3)敲降SW480细胞中FOXM1降低1,25(OH)2D3对β-catenin转录活性的抑制作用(P<0.05)。结论1,25(OH)2D3通过上调FOXM1的表达,发挥抑制β-catenin转录活性的作用。Objective To explore the inhibitory effect and mechanism of 1α,25-dihydroxyvitamin D3[1,25(OH)2D3]onβ-catenin transcriptional activity in human colon cancer cells.Methods Colon cancer cell line SW480 was treated with either 1,25(OH)2D3(100 nmol/L)or vehicle(control)for 48 hours,then several parameters were measured:the transcriptional activity ofβ-catenin by Dual-LuciferaseReporter Assay System;the nuclear protein expression level ofβ-catenin by Western blot;mRNA coding forβ-catenin and forkhead box M1(FOXM1)and the protein expression by RT-qPCR and Western blot.SW480 cells were subjected to transfecting siRNA to knock down FOXM1,followed by 1,25(OH)2D3 treatment and measurement of the transcriptional activity ofβ-catenin by Dual-LuciferaseReporter Assay System.Results 1)1,25(OH)2D3 significantly repressed the transcriptional activity ofβ-catenin in SW480 cells(P<0.05),while did not affect its mRNA and protein expression;2)1,25(OH)2D3 increased the protein expression of FOXM1(P<0.05);3)The inhibitory effect of the transcriptional activity ofβ-catenin by 1,25(OH)2D3 in SW480 cells was decreased when FOXM1 was knocked down(P<0.05).Conclusions 1,25(OH)2D3 represses the transcriptional activity ofβ-catenin via increasing FOXM1 expression.

关 键 词：1α 25-二羟基维生素D3 结肠癌 Β-CATENIN FOXM1 

分 类 号：R574.62[医药卫生—消化系统]